Endocrine Control of Calcium Metabolism Flashcards
State some roles of calcium in the body.
Control of neuromuscular excitability (hypocalcaemia leads to hyperexcitability because Ca2+ normally blocks the Na+ channels)
Muscle Contraction
Strength in bone
Blood coagulation (Factor IV)- calcium is Factor 4
Intracellular second messenger
Intracellular co-enzyme
Where is calcium mainly stored?
Bone - 99% is stored as hydroxyapatite (salt, calcium with phosphorus) crystals in bone
How is calcium present in the blood and what is the concentration of the total calcium ion? What is the main component?
-2.5 mM
Unbound ionised calcium (bioactive) - 50%
Bound to plasma proteins - 45% (1.13mM)
Tiny bit as soluble salts (0.13mM)
What is the usual daily intake of calcium?
1000 mg/day
What is the concentration of unbound ionised calcium in the blood?
1.25 mini Molar (mM), therefore this is the amount that is biologically active component.
What two hormones raise plasma calcium concentration?
- Parathyroid Hormone
- Calcitriol (1,25-dihydroxycholecalciferol) Vitamin D3
What hormone decreases plasma calcium concentration?
Calcitonin
Where is parathyroid hormone produced?
Parathyroid Glands (four of them) -
Where is calcitonin produced?
Parafollicular cells (between follicular cells of the thyroid gland) in the thyroid gland.
Describe the effects of parathyroid hormone on the kidneys.
Increases calcium reabsorption
Increases phosphate excretion
Describe the effects of PTH on bone.
Stimulates osteoclasts
Inhibits osteoblasts, this goes onto increase bone resorption.
Describe the effects of PTH on the small intestines.
PTH increases the activity of 1 alpha hydroxylase (in the kidneys), which is involved in the production of calcitriol, which increases calcium and phosphate absorption in the small intestine.
How does PTH increase calcium release from bone?
PTH has a direct effect in inhibiting osteoblasts. PTH makes the osteoblasts produce osteoclast activating factors (such as RANKL:Receptor activator of nuclear factor kappa-Β ligand) that bind to receptors on osteoclasts and stimulates the break down of bone matrix to release calcium.
What can stimulate PTH release?
Low plasma calcium concentration
Catecholamines (by binding to beta receptors)
Describe the negative feedback loops on PTH.
Increased plasma calcium concentration has a negative feedback effect on PTH
Calcitriol also has a negative feedback effect
What is the precursor of calcitriol?
Cholecalciferol
Where does this precursor come from?
-Diet
-Sun Light (UV light converts 7-dehydrocholesterol to cholecalciferol)
NOTE: cholecalciferol is VITAMIN D3
Describe the reactions that have to take place to convert the precursor to calcitriol.
Cholecalciferol travels to the liver where 25-hydroxylase converts it to 25-hydroxycalciferol, which is then stored in the liver.
It then moves to the kidneys where 1 alpha hydroxylase (stimlated by PTH) converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (calcitriol)
Describe the effects of calcitriol.
MAIN ACTION: stimulates calcium and phosphate absorption in the SMALL INTESTINE
Increased osteoblast activity on bone.
Kidneys - increases calcium and phosphate reabsorption
How does calcitriol and PTH decrease phosphate reabsorption in the kidney?
They block the sodium/phosphate cotransporter
Calcitriol does this via the action of FGF23 (fibroblast growth factor 23)
Describe the effects of calcitonin.
Calcitonin inhibits osteoclast activity
Calcitonin also affects the KIDNEYS - increase sodium excretion and hence increase urinary excretion of phosphate and calcium.
This decreases plasma calcium concentration
State a physiological benefit of calcitonin.
During pregnancy women need a higher plasma calcium concentration (e.g. for milk), calcitonin protects the bone from break down.
State three causes of hypocalcaemia.
Hypoparathyroidism: insufficient PTH
Pseudohypoparathyroidism: resistence to PTH
Vitamin D Deficiency
What two signs are used to demonstrate hypocalcaemia?
Trousseau’s Sign: put slight pressure on the arm and the hand can go into contraction
Chvostek’s Sign : tap the facial nerve at the angle of the jaw you get muscles to contract
These are both signs of tetany
What is pseudohypoparathyroidism and what are some clinical features?
Target organ resistance to PTH (also called Allbright Heriditary Osteodystrophy)
Round face, short, low IQ, short 4th metacarpal, hypothyroidism, hypogonadism
What does vitamin D deficiency cause in children and adults and what are the clinical feature?
Children - rickets
Adults - osteomalacia
Bowing of bones in children
Fractures in adults
State three causes of hypoparathyroidism
- idiopathic
- hympomagneseamia
- supression by raised calcium concentration
what are some diagnostic results in the different types of hypoparathyroidism
-in hypoparathyroidism you get an increase in plasma phosphate conc because PTH isn’t stimulating the excretion of phosphate from the kidneys. Decrease in plasma calcium and PTH
-pseudohypoparathyroidism- the parathyroid glands are producing insufficient PTH, but the target organs are resistent to PTH so plasma calcium conc is low and plasma phosphate and PTH increase
Vitamin D defiency: phosphate levels low, PTH normal and calcium low
State three causes of hypercalcaemia.
Primary hyperparathyroidism
Tertiary hyperparathyroidism
Vitamin D Toxicosis
Describe the differences between primary, secondary and tertiary hyperparathyroidism
Primary - caused by parathyroid adenoma producing huge amounts of PTH
Secondary - caused by other reasons e.g. renal excretion of Ca2+ ions leading to compensatory increase in release of PTH (this causes low Ca2+ because it is being lost from the kidneys)
Tertiary - initial chronic low plasma calcium concentration - parathyroid gland is massively stimulated for a long time and so PTH production becomes autonomous and stops responding to negative feedback (leads to hypercalcaemia in primary and teritary)
State some consequences of parathyroid hormone excess.
Kidney stones (calcium deposits) Increased risk of fracture
What is a distinctive clinical feature of primary hyperparathyroidism?
Clubbing of the fingers
Describe how calcium level are detected in the body?
It is detected by calcium sensing receptors which are found in the parathyroid gland and the renal tubules of the kidney.
Describe how PTH is formed and how it goes on to effect?
- Initially synthesized as protein pre-proPTH
- PTH is a polypeptide of 84 amino acids
- Binds to transmembrane G-protein linked receptors
- Activation of adenyl cyclase, but also probably PLC as second messenger systems
Describe how calcitonin is formed and how it goes on to effect?
- Synthesized as pre-procalcitonin
- Calcitonin is 32 amino acid polypeptide
- Binds to transmembrane G-protein linked receptor
- Activation of adenyl cyclase or PLC as second messenger systems
